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Activity: Herbicide (uracil)
Structure:

Adverse Effects:
Blood
Body Weight Decrease
Bone
Liver
Spleen

Blood (click on for all fluorinated pesticides)

The most susceptible species in long term studies was the mouse. A NOEL for butafenacil-allyl of 0.36 mg/kg bw/day was found for males in an 18 month study, essentially based on haematological effects mostly in males and liver toxicity in animals of both sexes. A rat 2-year study revealed a NOEL of 1.14 mg/kg bw/day for males, based on liver toxicity in animals of both sexes. A safety factor of 100 is considered appropriate for the ADI, due to the extensive toxicology database for butafenacil-allyl. This results in an ADI of 0.004 mg/kg bw/day (p 10).
-- Long-Term Studies. Mice received butafenacil in the diet at concentrations of 0, 1, 3, 10 and 60 ppm over 18 months. Haematological effects included lower mean values for erythrocyte count, haemoglobin concentration and haematocrit in males at 60 ppm at weeks 53 and 79, respectively, and for erythrocyte count, haemoglobin and haematocrit at week 79 in males at 10 ppm. Males also had slightly increased neutrophil and monocyte counts at 60 ppm, and a slight thrombocytosis. Mean absolute and relative liver weights were increased in both sexes at 60 ppm. The incidence of enlarged liver was increased in males at 60 ppm and in females at 10 and 60 ppm. Microscopic examination revealed an increased incidence of hepatocyte necrosis and hyperplasia of Kupffer cells in the liver of males at 10 and 60 ppm, and of females at 60 ppm. In addition, an increased incidence of lipofuscin deposition, and inflammatory cell infiltration was seen in males at 60 ppm. There was no treatment-related increase in the incidence of neoplasms at any dose. Butafenacil was not carcinogenic in mice. The NOEL was 3 ppm in males and 10 ppm in females, equivalent to 0.36 and 1.20 mg/kg bw/day for males and females, respectively (p7-8)....
Ref: Public Release Summary on Evaluation of the new active BUTAFENACIL in the products LOGRAN B-POWER HERBICIDE & TOUCHDOWN B-POWER HERBICIDE. National Registration Authority for Agricultural and Veterinary Chemicals. Australia. February 2002. Available at:
http://www.nra.gov.au/publications/prsbuta.pdf

Some excerpts from Table 3.--Toxicological Dose and Endpoints for Butafenacil - a summary of the toxicological endpoints used for human risk assessment Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
-- Exposure Scenario -- Dose Used in Risk Assessment, UF -- Special FQPA SF* and Level of Concern for Risk Assessment	Study and Toxicological Effects
-- Chronic dietary (All populations) -- NOAEL= 1.2 mg/kg/day UF = 100 -- Chronic RfD = 0.012 mg/ kg/day. -- Special FQPA SF = 1 cPAD = chronic RfD -- Special FQPA SF = 0.012 mg/kg/day.	Mouse oncogenicity study. The LOAEL is 6.96 mg/kg/. day, based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males
-- Short-term inhalation (1 to 30 days) -- Oral NOAEL = 18.8 mg/kg/ day -- Residential LOC for MOE = 100 -- Occupational = 100	90-day rat feeding study. The LOAEL for this study is 62.3 mg/kg/ day based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity
-- Short-term incidental oral (1 to 30 days) -- Intermediate-term incidental oral (1- 6 months) -- LOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = NA	90-day rat feeding study. The LOAEL for this study is 62.3 mg/kg/ day, based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity
-- Short-term inhalation (1 to 30 days) -- Intermediate-term inhalation (1 to 6 months) -- Oral NOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = 100	Same as above

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (dietary) toxicity rodents (rat) - [870.3100]	NOAEL = 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F) based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration
90-Day oral (capsule) toxicity in non- rodents (dog) - [870.3150]	NOAEL = 200 mg/kg/ day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreases in MCV and MCH in males; increases in RDW, HDW, platelets and triglycerides in males; and hemosiderosis in spleen and liver and extramedullary hematopoiesis the spleen in males
1-Year chronic oral (capsule) toxicity (dog) - [870.4100]	NOAEL = 500 mg/kg/day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreased body weight gain in males, decreased MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC); increased thrombocytes and red cell volume distribution width; hepatic histopathology: glycogen disposition, inclusion bodies in cytoplasm, and pigment disposition in both sexes, and focal vaculolation in females
18-Month carcinogenicity dietary study (mouse) - [870.4200]	NOAEL = 10 ppm (1.17/1.20 mg/kg/day M/F) LOAEL = 60 ppm (6.96/ 6.59 mg/kg/day M/ F), based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males No evidence of carcinogenicity
Mechanistic studies - [870.7485]	Effects on enzymes of cultured mouse, rat, and/or human hepatocytes involved with heme biosynthesis
Mechanistic studies - [870.7485]	Effects on liver microsomal and plasma protox activity and its metabolic conversion
Mechanistic studies - [870.7485]	Effects on porphyrin profile in rats; treatment induced porphyria, consisting of accumulation of selected porphyrins in the liver, spleen, and plasma and increased excretion in urine and feces
Mechanistic studies - [870.7485]	Test substance interferes with heme biosynthesis in rats, as evidenced by dose- dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system

Body Weight Decrease (click on for all fluorinated pesticides)

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (dietary) toxicity rodents (rat) - [870.3100]	NOAEL = 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F) based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration
2-Generation reproduction and fertility effects - [870.3800]	Parental/systemic NOAEL = 30 ppm (2.4/ 2.5 mg/kg/day M/F) Parental/systemic LOAEL = 300 ppm (23.8/25.2 mg/kg/ day M/F), based on decreased body weights and food consumption and on increased incidences of bile duct hyperplasia and liver necrosis in males and females of both generations Offspring NOAEL = 300 ppm (23.8/25.2 mg/kg/day M/F) Offspring LOAEL = 1,000 ppm (79.6/ 83.8 M/F), based on decreased pup body weight and body weight gain in both generations Reproductive NOAEL = 30 ppm (2.4/2.5 mg/ kg/day M/F) Reproductive LOAEL = 300 ppm (23.8/25.2 mg/kg/day M/F) based on an increase in the number of days to mating in both generations
1-Year chronic oral (capsule) toxicity (dog) - [870.4100]	NOAEL = 500 mg/kg/day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreased body weight gain in males, decreased MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC); increased thrombocytes and red cell volume distribution width; hepatic histopathology: glycogen disposition, inclusion bodies in cytoplasm, and pigment disposition in both sexes, and focal vaculolation in females

Bone (click on for all fluorinated pesticides)

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (dietary) toxicity rodents (rat) - [870.3100]	NOAEL = 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F) based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration

Some excerpts from Table 3.--Toxicological Dose and Endpoints for Butafenacil - a summary of the toxicological endpoints used for human risk assessment Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
-- Exposure Scenario -- Dose Used in Risk Assessment, UF -- Special FQPA SF* and Level of Concern for Risk Assessment	Study and Toxicological Effects
-- Short-term inhalation (1 to 30 days) -- Oral NOAEL = 18.8 mg/kg/ day -- Residential LOC for MOE = 100 -- Occupational = 100	90-day rat feeding study. The LOAEL for this study is 62.3 mg/kg/ day based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity
-- Short-term incidental oral (1 to 30 days) -- Intermediate-term incidental oral (1- 6 months) -- LOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = NA
-- Short-term inhalation (1 to 30 days) -- Intermediate-term inhalation (1 to 6 months) -- Oral NOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = 100

Liver (click on for all fluorinated pesticides)

-- The most susceptible species in long term studies was the mouse. A NOEL for butafenacil-allyl of 0.36 mg/kg bw/day was found for males in an 18 month study, essentially based on haematological effects mostly in males and liver toxicity in animals of both sexes. A rat 2-year study revealed a NOEL of 1.14 mg/kg bw/day for males, based on liver toxicity in animals of both sexes. A safety factor of 100 is considered appropriate for the ADI, due to the extensive toxicology database for butafenacil-allyl. This results in an ADI of 0.004 mg/kg bw/day (p 10).
Long-Term Studies. Mice received butafenacil in the diet at concentrations of 0, 1, 3, 10 and 60 ppm over 18 months. Haematological effects included lower mean values for erythrocyte count, haemoglobin concentration and haematocrit in males at 60 ppm at weeks 53 and 79, respectively, and for erythrocyte count, haemoglobin and haematocrit at week 79 in males at 10 ppm. Males also had slightly increased neutrophil and monocyte counts at 60 ppm, and a slight thrombocytosis. Mean absolute and relative liver weights were increased in both sexes at 60 ppm. The incidence of enlarged liver was increased in males at 60 ppm and in females at 10 and 60 ppm. Microscopic examination revealed an increased incidence of hepatocyte necrosis and hyperplasia of Kupffer cells in the liver of males at 10 and 60 ppm, and of females at 60 ppm. In addition, an increased incidence of lipofuscin deposition, and inflammatory cell infiltration was seen in males at 60 ppm. There was no treatment-related increase in the incidence of neoplasms at any dose. Butafenacil was not carcinogenic in mice. The NOEL was 3 ppm in males and 10 ppm in females, equivalent to 0.36 and 1.20 mg/kg bw/day for males and females, respectively (p7-8).... Rats were administered butafenacil in the diet at doses of 0, 10, 30, 100 and 300 ppm for 24 months. At interim sacrifice, the incidence and/or severity of liver necrosis was increased in both sexes at 100 and 300 ppm. In addition, increased incidence of hepatocellular single cell necrosis (300 ppm) and increased incidence (100 and 300 ppm) and severity (300 ppm) of cholangiofibrosis were noted in females. At the end of the study, higher incidences and slightly increased severity of fatty change in the liver, and slightly higher incidences of increased mitotic activity of hepatocytes were observed in females at 300 ppm. There was no treatment-related increase in the incidence of neoplasms at any dose. Butafenacil was not carcinogenic in rats. The NOEL was 30 ppm, equivalent to 1.14 mg/kg bw/day for males and 1.30 mg/kg bw/day in females, respectively... Butafenacil was administered to rats in the diet at concentrations of 0, 100, 300 and 1,000 ppm for a period of 90 days. Observations and functional tests conducted during the Functional Observation Battery did not show any effects of toxicological significance. No morphological changes in the central or peripheral nervous system were revealed at neuropathological examination. Microscopic examination of the liver showed inflammatory cell infiltration, cholangiofibrosis of the intrahepatic bile ducts, pigments within Kupffer cells, necrosis of single hepatocytes, cytoplasmic vacuolation, hypertrophy of centrilobular hepatocytes, and an increased mitotic activity of hepatocytes of males at 1,000 ppm. Slight effects were seen at 300 ppm, indicating the beginning of liver necrosis.
Ref: Public Release Summary on Evaluation of the new active BUTAFENACIL in the products LOGRAN B-POWER HERBICIDE & TOUCHDOWN B-POWER HERBICIDE. National Registration Authority for Agricultural and Veterinary Chemicals. Australia. February 2002.
http://www.nra.gov.au/publications/prsbuta.pdf

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (dietary) toxicity rodents (rat) - [870.3100]	NOAEL = 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F) based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration
90-Day oral (dietary) toxicity in rodents (mouse) - [870.3100]	NOAEL = 30 ppm (4.11/5.67 mg/kg/day M/F) LOAEL = 100 ppm (13.8/20.1 mg/kg/ day M/F), based on hepatic histopathology: fatty change, glycogen deposition, and hypertrophy in both sexes
90-Day oral (capsule) toxicity in non- rodents (dog) - [870.3150]	NOAEL = 200 mg/kg/ day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreases in MCV and MCH in males; increases in RDW, HDW, platelets and triglycerides in males; and hemosiderosis in spleen and liver and extramedullary hematopoiesis the spleen in males
1-Year chronic oral (capsule) toxicity (dog) - [870.4100]	NOAEL = 500 mg/kg/day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreased body weight gain in males, decreased MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC); increased thrombocytes and red cell volume distribution width; hepatic histopathology: glycogen disposition, inclusion bodies in cytoplasm, and pigment disposition in both sexes, and focal vaculolation [liver] in females
18-Month carcinogenicity dietary study (mouse) - [870.4200]	NOAEL = 10 ppm (1.17/1.20 mg/kg/day M/F) LOAEL = 60 ppm (6.96/ 6.59 mg/kg/day M/ F), based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males No evidence of carcinogenicity
Combined 2-Year chronic/ carcinogenicity dietary study (rat) - [870.4300]	NOAEL = 100 ppm (3.76/4.43 mg/kg/ day M/F) LOAEL = 300 ppm (11.4/13.0 mg/kg/ day M/F), based on minimal hepatic abnormalities in the females, including a fatty change and increased mitotic activity No evidence of carcinogenicity
Mechanistic studies - [870.7485]	Effects on enzymes of cultured mouse, rat, and/or human hepatocytes involved with heme biosynthesis
	Effects on liver microsomal and plasma protox activity and its metabolic conversion
	Effects on porphyrin profile in rats; treatment induced porphyria, consisting of accumulation of selected porphyrins in the liver, spleen, and plasma and increased excretion in urine and feces
	Test substance interferes with heme biosynthesis in rats, as evidenced by dose- dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system

Some excerpts from Table 3.--Toxicological Dose and Endpoints for Butafenacil - a summary of the toxicological endpoints used for human risk assessment Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
-- Exposure Scenario -- Dose Used in Risk Assessment, UF -- Special FQPA SF* and Level of Concern for Risk Assessment	Study and Toxicological Effects
-- Chronic dietary (All populations) -- NOAEL= 1.2 mg/kg/day UF = 100 -- Chronic RfD = 0.012 mg/ kg/day. -- Special FQPA SF = 1 cPAD = chronic RfD -- Special FQPA SF = 0.012 mg/kg/day. -- Long-term inhalation (>6 months) -- Oral NOAEL = 1.2 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = 100	Mouse oncogenicity study. The LOAEL is 6.96 mg/kg/. day, based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males

Spleen (click on for all fluorinated pesticides)

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (capsule) toxicity in non- rodents (dog) - [870.3150]	NOAEL = 200 mg/kg/ day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreases in MCV and MCH in males; increases in RDW, HDW, platelets and triglycerides in males; and hemosiderosis in spleen and liver and extramedullary hematopoiesis the spleen in males
Mechanistic studies - [870.7485]	Effects on porphyrin profile in rats; treatment induced porphyria, consisting of accumulation of selected porphyrins in the liver, spleen, and plasma and increased excretion in urine and feces
	Test substance interferes with heme biosynthesis in rats, as evidenced by dose- dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system